Adrenal sparing giant adrenal cyst excision by 3D laparoscopic approach: a case report

Adrenal cyst is rare clinical entity. Usually they are asymptomatic, non-functional, <10 cm in size and often discovered incidentally. We report a left adrenal cyst in 58-year-old woman measuring 23 cm in diameter, displacing left kidney infero-medially and pancreas anteriorly, because of its huge size. She presented with left flank pain over a 6-month period. Serial abdominal ultrasound and CT imaging revealed left suprarenal cystic mass of size 10 cm to begin with and gradually increased to size of 23 cm over period of 10 years when she became symptomatic. All laboratory and endocrine function tests were normal. 3D laparoscopic surgery done and cyst was completely removed with preservation of adrenal gland. Histopathological examination revealed a benign endothelial adrenal cyst. The postoperative course was uneventful and patient had no evidence of recurrence during follow-up. The giant adrenal cysts are relatively rare and represent great surgical challenge during resection.

Optimization of advanced manufacturing processes using socio inspired cohort intelligence algorithm

The demand of Advanced Machining Processes (AMP) is continuously increasing owing to the technological advancement. The problems based on AMP are complex in nature as it consisted of parameters which are interdependent. These problems also consisted of linear and nonlinear constraints. This makes the problem complex which may not be solved using traditional optimization techniques. The optimization of process parameters is indispensable to use AMP's at its aptness and to make it economical to use. This paper states the optimization of process parameters of Ultrasonic machining (USM) and Abrasive water jet machining (AWJM) processes to maximize the Material Removal Rate (MRR) using a socio inspired Cohort Intelligent (CI) algorithm. The constraints involved with these problems are handled using static penalty function approach. The solutions are compared with other contemporary techniques such as Particle Swarm Optimization (PSO), Artificial Bee Colony (ABC), Modified Harmony Search (HS_M) and Genetic Algorithm (GA)

A phase 1 first‐in‐human study of GS‐0189, an anti‐signal regulatory protein alpha (SIRPα) monoclonal antibody, in patients with relapsed/refractory (R/R) non‐Hodgkin lymphoma (NHL)

Abstract Signal regulatory protein alpha (SIRPα) is the receptor for cluster of differentiation (CD)47, a potent “don't eat me” signal for macrophages. Disruption of CD47‐SIRPα signaling in the presence of prophagocytic signals can lead to enhanced phagocytosis of tumor cells, resulting in a direct antitumor effect; agents targeting this pathway have shown efficacy in non‐Hodgkin lymphoma (NHL) and other tumor types. GS‐0189 is a novel anti‐SIRPα humanized monoclonal antibody. Here we report: (1) clinical safety, preliminary activity, and pharmacokinetics of GS‐0189 as monotherapy and in combination with rituximab from a phase 1 clinical trial in patients with relapsed/refractory NHL (NCT04502706, SRP001); (2) in vitro characterization of GS‐0189 binding to SIRPα; and (3) in vitro phagocytic activity. Clinically, GS‐0189 was well tolerated in patients with relapsed/refractory NHL with evidence of clinical activity in combination with rituximab. Receptor occupancy (RO) of GS‐0189 was highly variable in NHL patients; binding affinity studies showed significantly higher affinity for SIRPα variant 1 than variant 2, consistent with RO in patient and healthy donor samples. In vitro phagocytosis induced by GS‐0189 was also SIRPα variant–dependent. Although clinical development of GS‐0189 was discontinued, the CD47‐SIRPα signaling pathway remains a promising therapeutic target and should continue to be explored

Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis.

INTRODUCTION:Randomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial. METHODS:Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules. RESULTS:Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001). CONCLUSIONS:Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy

Additional information on the threatened Cryptocoryne cognata Schott (Araceae): A need for reassessment of the IUCN Red List status

Cryptocoryne cognata Schott is a threatened species distributed in the entire Konkan stretch covering Goa, Karnataka and Maharashtra. It was rediscovered in 1990 after not being documented for one and half centuries. The data concerning its morphology, distribution and ecological preferences are presented in this paper in order to contribute to the Global Strategy for Plant Conservation (GSPC) goals and to assist taxonomists in assessing and protecting this species from extinction in future.   </div

The Revised International Prognostic Scoring System "Molecular" (IPSS-Rm), a Validated and Dynamic Model in Treated Patients with Myelodysplastic Syndromes (MDS)

Abstract Background The Revised International Prognostic Scoring System (IPSS-R) was developed to risk stratify untreated patients (pts) with myelodysplastic syndromes (MDS). It has since been validated in pts treated with a single line of therapy; however, these approaches do not reflect typical MDS pts who receive different types of treatment in different sequences. Recently, genome sequencing technologies have identified recurrent somatic mutations that impact survival in MDS. We propose and validate a modification to the IPSS-R to include mutational data that can improve its predictive power at diagnosis regardless of the initial or subsequent therapies and at any time during the disease course. Methods Clinical and mutational data from MDS pts diagnosed between 1/2000-1/2012 were analyzed. A panel of 62 gene mutations obtained by next generation targeted deep sequencing which has been described as recurrent mutations in myeloid malignancies was included. Pts who underwent hematopoietic cell transplant (HCT) were censored at the time of transplant. A Cox proportional multivariate analysis including age, IPSS-R score and mutations that are present in > 10 pts was used to select independent prognostic factors. The fit of the proposed model to the data was assessed by using the concordance (c-) index. Results A total of 508 pts were included and divided into two cohorts, training (333 pts, used to build the new model), and validation (175 pts, used to validate it). Median age of the training cohort was 68 years (range, 20-87); 214 pts (64%) had de novo MDS, 39 (12%) had prior antecedental hematologic disorders, 37 (11%) secondary MDS, and 43 (13%) had chronic myelomonocytic leukemia. Pts received 0-7 lines of therapy: 15% did not receive any treatment, 85% received at least one treatment, 40% received > 2 treatments, 20% received > 3 treatments and 14% underwent HCT. First line therapies included: growth factors (30%), azacitidine+/- combinations (32%), decitabine+/- combinations (7%), lenalidomide (5%), investigational agents (5%), chemotherapy (2%), and immunosuppressive therapy (4%). Per IPSS-R, median OS for very low, low, intermediate, high, and very high was 35.5, 31.8, 19.1, 17.9, and 6.9 months (m), respectively, Figure1A. To minimize bias in pt selection, the validation cohort samples were randomly selected and sequenced after the development of the new model. Among the 62 gene mutations, 24 were present in > 10 pts in the training cohort: TET2 (17%), ASXL1 (15%), SF3B1 (14%), STAG2 (11%), DNMT3A (11%), RUNX1 (10%), U2AF1 (9%), GPR98 (8%), ZRSR2 (7%), BCOR (6%), TP53 (5%), NF1 (5%), EZH2 (5%), APC (5%), SUZ12 (5%), CBL (4%), PRPF8 (4%), NRAS (3%), CUX1 (3%), DDX54 (3%), IDH1 (3%), KDM6A (3%), PHF6 (3%), and SETBP1 (3%). A cox proportional hazard analysis including age, IPSS-R score, and the 24 genes mutations listed above identified the following as independent prognostic factors: age, IPSS-R, EZH2, SF3B1, and TP53. The linear predictive Cox model score obtained using the fitted coefficients of each prognostic factor wasage x.04 + IPSS-R score x.3 + EZH2 x.7 + SF3B1 x.5 + TP53 x 1 which translated to 4 prognostic groups: low, intermediate-1, intermediate-2, and high with median OS of 37.4, 23.2, 19.9, and 12.2 m, respectively, p< .001, Figure1B with significant improvement in the C-index of the new model (.74) observed compared to the IPSS-R (.57). The model was then applied to the validation cohort with significant ability to distinguish prognostic groups for OS (p<.0001) (Figure1C) despite differences between training and validation cohorts in IPSS-R risk categories (p =.04) and treatment history. To validate whether the new model can be applied at any time during disease course, we sequenced paired samples from 53 MDS pts at different time points (diagnosis, after treatment failure, and at the time of AML progression). The median time from diagnosis to sample 1 was 5.6 m (range, 0-56) and to sample 2 was 18.2 m (range, 5-94.6). The new model was able to predict the OS at each time point (Figure 1D shows IPSS-Rm at sample1 and 1E at sample2). Conclusion We propose a modification of the IPSS-R scoring system that incorporates mutational data and enhances its predictive ability in pts with MDS regardless of initial or subsequent treatments. This model is dynamic and valid at varying time points of a pt's disease course. Figure 1. OS by IPSS-R and IPSS-Rm in training, validation, and paired samples cohorts Figure 1. OS by IPSS-R and IPSS-Rm in training, validation, and paired samples cohorts Disclosures Sekeres: TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees